Liver metastases from uveal melanoma are usually fatal. Our previous experience with more than 100 patients with liver metastases indicates that the median survival after development of liver metastasis was 3 months. One of the unique characteristics of metastatic uveal melanoma is that liver is the most common site of metastases and often is the only site of metastases. The clinical course of patients with uveal melanoma is dominated by progression of the disease in the liver. We have developed a novel treatment for liver metastasis; Immunoembolization of the hepatic artery with granulocyte-macrophage colony stimulating factor (GM-CSF). By using this approach, (1) tumor cells are killed by the ischemic effect of embolization, (2) local immunological reactions would be facilitated by GM-CSF, and (3) systemic immunity against tumor cells could develop. The phase I clinical trial of immunoembolization with GM-CSF in uveal melanoma patients demonstrated prolongation of survival and inflammatory responses in distant metastases. In the proposed randomized phase II clinical trial, uveal melanoma patients with liver metastases will be randomized to receive either immunoembolization with GM-CSF or plain embolization without GMCSF. In specific aim (1), we will determine whether immunoembolization with GM-CSF produces clinical benefit. The response in the liver metastases, time to progression of disease and overall survival will be investigated. In specific aim 2), we will determine whether immunoembolization of the liver induces an immune response. Composition and function of cells infiltrating the liver metastasis will be assessed before and after embolization treatment. We also investigate a systemic immune response to melanoma by checking T cell responses to melanoma-related antigens. We also investigate development of antibodies to melanoma-related gangliosides. The results of immunological tests will be compared to those obtained from patients who are treated with plain embolization.